Apparatus for analysing liquid substances likely to form agglutinates

ABSTRACT

An annular planar shaped support for a multiplicity of vessels containing liquid samples to be analyzed for use as part of a liquid chemical or biochemical analyzing machine. The support has a multiplicity of perforations therein for receiving the vessels. The perforations are disposed angularly and radially throughout substantially the entire area of the support. Each of the vessels are cupola-shaped with opaque side walls and a transparent bottom. The support includes a central opening having a radial cut out for positioning the support to a shaft on the machine.

United States Patent [191 Matte 1 APPARATUS FOR ANALYSING LIQUID SUBSTANCES LIKELY TO FORM AGGLUTINATES [75] Inventor: Claude Matte, Paris, France [73] Assignees: Centre National de la Recherche Scientil'ique; Centre National de Transfusion Sanquine, Paris, France; a part interest to each [22] Filed: Sept. 4, 1973 [21] Appl. No.: 393,996

Related U.S. Application Data [63] Continuation of Ser. No. 163,936, July 19, 1971, abandoned. which is a continuation of Ser. No. 728,189, May 9, 1968, Pat, No. 3,617,222.

[30] Foreign Application Priority Data May 12, 1967 France 67,106180 Mar. 22, 1968 France 68.145043 [52] U.S. Cl. 23/259; 23/253 R; 23/230 B; 356/246 [51] Int. Cl G0ln 33/16; GOln 1/14 [58] Field of Search 23/253, 259, 230, 292; 356/246 {56] References Cited UNITED STATES PATENTS 3,192,968 7/1965 Baruch et al. 23/259 X 1 May 13,1975

3,350,946 11/1967 lsreeli 23/253 3,449,959 6/1969 Grimshaw 23/259 UX 3,532,470 10/1970 Rochte 23/253 3,540,858 10/1970 Rochte et al. 23/253 X 3,555,284 l/l971 Anderson 23/259 UX 3,565,582 2/1971 Young 23/253 X 3,589,867 6/1971 Heinz et a1....... 23/253 3,680,967 8/1972 Engelhardt 23/253 Primary ExaminerR. E. Serwin Attorney, Agent, or Firm-Stevens, Davis, Miller & Mosher [57] ABSTRACT An annular planar shaped support for a multiplicity of vessels containing liquid samples to be analyzed for use as part of a liquid chemical or biochemical analyzing machine. The support has a multiplicity of perforations therein for receiving the vesselsv The perforations are disposed angularly and radially throughout substantially the entire area of the support. Each of the vessels are cupola-shaped with opaque side walls and a transparent bottom. The support includes a central opening having a radial cut out for positioning the support to a shaft on the machine.

2 Claims, 36 Drawing Figures FATEMEQHAY 1 35m SHEET CHUF 10 SHEET CSUF 1O SHEEI NIH] Hid I 3 i375 FIE wk! um wm mm mm a.

m ww i mm A v m an a E Q R m a w m Q s H. q Q R 5 I %m w I w o .o\ 10 ,0 0 X: ,3. U Q

PHENIEB RAY I 3 i975 SHEU 10a? 10 1 APPARATUS FOR ANALYSING LIQUID SUBSTANCES LIKELY TO FORM AGGLUTINATES This application is a continuation of my co-pending application Ser. No. l63,936, filed .luly l9, l97l now abandoned. which is a continuation of my co-pending application Ser. No. 728,l89, filed May 9, 1968 now US. Pat. No. 3,617,222.

The present invention relates to a method and apparatus for analysing liquid substances likely to form, with certain appropriate reagents. agglutinates. Generally, when these occur. they are of varying sizes and one can distinguish microagglutinates (not visible to the naked eye) and macroagglutinates (visible to the naked eye).

Such a method and such a device are, of course, particularly well adapted to the determination of erythrocyte types and plasma blood groups, to sero-diagnosis of certain illnesses such as typhoid and syphilis, and to the detection of the rheumatoid factor by means of sensitized particles as, for example, latex of polystyrene.

The present invention enables an automatic examination of reactions to be carried out with a view to determining certain characteristics which are useful in hematology, serology, bacteriology or chemistry and more particularly to determine blood groups, automation serving essentially to minimize risk of errors in inter pretation and transcription of results, whilst sensitivity and speed of reactions are increased.

Thus, for example, determination of a blood group for an individual is carried out by means of several complementary reactions each using an agglutination of red cells. For some of these, the red cells of the per son being examined are placed in contact with a series of reagents called test-serums" which are serums which each agglutinate a well defined and different kind of cell.

For other reactions, the serum of the patient is placed in contact with a series of test-cells," that is those where the group is already known. The various combinations of agglutination or non-agglutination which finally occur in the two series of reactions each define a blood group.

Cells never agglutinate entirely. Some free cells always remain in a greater or lesser quantity. Their presence, when they are suspended in a liquid substance, gives to the latter a turbidity which can be measured photometrically (if steps are taken not to be hindered by opacity due to the agglutinated cells themselves). This turbidity is obviously dependent upon the number of cells per unit of volume: the greater the agglutination, the greater the transparency of the medium in which the agglutinated material rests.

The invention enables agglutinations to be detected either by nephelometry if a very small quantity of reactive cells have been used, or by opacimetry if a fairly strong dose of cells has been used. This opacimetry can be obtained either on a peripheral annular zone of the reaction vessel or on a small central zone, it being understood that the more intense the agglutination the more cells are collected in the centre of the reaction vessel and the more transparent is the peripheral zone.

The method of this invention is characterized by having, in a cup with a transparent bottom, preferably concave in shape, the liquid substance to be analysed, with at least one reagent added with which it is susceptible of forming agglutinates, and subjecting this to at least two successive agitations, the first having a greater speed and the second a slower speed than a critical speed over and under which the macro-agglutinates are respectively dispersed in the medium then collected near the centre of the said transparent bottom, after which is measured by turbidimetry, that is by opacimetry (and/or nephelometry), and approximately in parallel relationship to an orthogonal axis to said bottom near the centre thereof, the opacity of the central and- /or peripheral part of the said substance. Preferably the cup has a rotational symmetry axis and the shape of a brandy glass, that is a cupula shaped bottom connected to inclined sides parting from the symmetry axis of the said cup, so that the latter has an enlarged part near the said bottom.

The method of this invention is based on the discovery of this critical speed which exists for media in which agglutinates appear which are denser than the liquid in which they are contained and which depends on nu merous parameters such as the nature and viscosity of the medium, the size of the agglutinates, the dimensions of the cup and its shape, etc. However, it is possible to determine this speed for each particular case experimentally.

Thus, in an apparatus according to the invention, that is having an agitation with two speeds at least, one being greater and the other less than the said critical speed corresponding to the substance to be analysed, the agitator may comprise a turn-table which is subjected to motion around a circle of diameter 1.10 inches (28 mm), whilst the vessel is in the shape of a brandy glass having an internal maximum diameter of approximately 0.62 inches 16 mm) for an aperture diameter of 0.31 inches (8 mm) and a height of about 0.78 inches (20 mm) this cup containing a blood of which the blood group has to be determined, this critical speed is found to be around rpm; the higher and lower speeds of the agitator can then be respectively and 60 rpm. Obviously these higher and lower speeds can vary greatly in terms of duration of movement.

The agitation at a speed higher than the critical speed disperses the particles uniformly (cells or others) stuck together or not, whereas the agitation at the speed which is less than the critical speed collects, with the aid of gravity, macro-agglutinates near the centre of the bottom of the cup. Optionally, the particles may be collected together to form a deposit by means of a centrifuge.

It has been found moreover that, after the first two agitations, a third at a speed less than that of the critical speed but closer to it than the speed of the second agitation, enables microagglutinates to be collected in the centre at the bottom of the vessel.

These microagglutinates which are not visible before the third agitation become so during this process, uniting together to form an opaque and visible spot.

In the methods known prior to the invention, in order to analyse a liquid medium susceptible of forming agglutinates in the presence of reagents, it was necessary to pour substance and reagent into a test tube-like vessel and wait for the agglutinates to form and settle and to measure, generally by opacimetric measurements, through the sides of the vessel, the liquid covering the settled agglutinates. Such a method generally requires a large amount of liquid substance and reagent so that the height and thickness of the liquid covering the agglutinates is sufficient to enable useful measurements to be taken, and each analysis takes a considerable time (at least half an hour) as measurements can only be made after complete sedimentation. This method is therefore unsuitable for automatic rapid and economic sampling and testing.

On the other hand. the method described in the invention enables each individual reaction to be carried out in a few seconds and does not require a lot of the substance to be analysed or a lot of reagent.

Moreover, such a known method cannot also measure by opacimetric measurements the contents of the vessel through its bottom. For if the middle of the vessel should contain some visible dispersed agglutinates, the transparency of the remainder should increase and yet with the known method the increase is imperceptible if the reagent is very dilute. Also, when the substance contains many visible agglutinates, the transparency of the remainder increases, but the agglutinates settle and cover the bottom of the vessel, rendering it opaque. One cannot therefore find a significant law between the quantity of light absorbed in passing into the vessel and the proportion of agglutinates formed. Also, when these agglutinates are large and form a kind of cut-up slab, the measurements are just as hazardous since, according to the hazards of the dispersion, large agglutinates can, at the moment of being measured by opacimetric measurements, either be side by side and thus absorb a lot of the light going through the substance, or be superimposed or overlapping and thus absorb less light. Thus, as in the previous case, the amount of light absorbed in going through the vessel is not indicative of the proportion of agglutinates formed.

On the other hand, the invention remedies all such difficulties by avoiding the phenomena mentioned above which make measurements either uninterpretable or not sensitive enough.

By means of the second agitation, all visible agglutinates are collected in the middle at the bottom of the cup. The third agitation also gathers in the centre of the said concave bottom the non visible microagglutinates, whose size is nevertheless greater than that of the particles of the initial substance to be analysed. Thus, an opacimetric measurement in the central zone of the bottom makes it possible to detect accurately the presence of agglutinates, even if they are few in number and not detectable (visually or photometrically) individually. Thus, any absorption of light corresponding to a measurement in the central area corresponds to the formation of agglutinates. Such a measurement can therefore give an information all or nothing: no absorption or an absorption which is less than a given threshold chosen as significant in terms of the material used means no formation of agglutinates, whereas an absorption greater than this threshold shows that there is formation of agglutinates.

A photometric measurement in the peripheral zone of the bottom makes it possible to obtain a quantitative result. Since there only remains in a peripheral zone of the vessel containing the mixture, after the second and a fortiori after the third agitation, very small particles, which are very numerous and are dispersed in a homogeneous manner. Therefore the hazardous character of measurements with overlapping of agglutinates (as mentioned above) disappears completely. Also, after the third agitation, all the microagglutinates are also displaced from the peripheral field of measurement and their parasitic opacity disappears with the difficulties specified above. So, in such conditions, in a system of rectangular coordinates, variations of absorption of a peripheral luminous bear are given on the Y-axis and the quantity of reagent introduced in the cup (related to the increase in number of agglutinates) on the X- axis, giving a continuous graph having three linear sections, th two end ones being practically parallel to the X-axis and the middle section being at an angle. Thus for a quantity of reagents falling within the limits of this middle section there is a simple ratio between quantity of light absorbed and quantity of reagent introduced in the vessel. Therefore, when working within this section of the graph, it is possible to carry out quantitative measurements with reference to known media.

The description which follows with diagrams attached given as a non-restrictive example, shows how the invention can be used, particularities shown on the diagram and in the text being, of course, part of the invention.

This description is more particularly directed towards the analysis of blood groups, but of course the invention is not restricted to this single type of analysis.

FIG. 1 shows a known blood sampling kit to which is attached a card with perforations on which are printed identification elements and various other information.

FIG. 2 is a diagrammatic view in perspective showing a device covered by this invention.

FIG. 3 shows, in perspective, a tube which will contain the sample of blood to be analysed, this tube being made as described in the invention.

FIG. 4 shows an enlargement of a fragment of the crown of the turn-table which will hold, in a given order, all the tubes of samples.

FIG. 5 is a vertical view along line V-V of FIG. 4.

FIG. 6 shows, in perspective, a fragment of the turntable holding the tubes of samples.

FIG. 7 is a cross section of a turn-table with cups set out in groups, each having the number of cups corresponding to the estimated number of reactions for the analysis of the blood taken from a sample tube.

FIGS. 8 and 9 are sections along lines VIII-VIII and IX-IX of FIG. 7 respectively.

FIGv I0 is a cross section, magnified, showing how the grooves are used to introduce into each of the cups of a section blood and reagents.

FIG. 11 is a vertical section along line XIXI of FIG. 10.

FIGS. 12a, 12b and [2c are vertical sections showing various ways of placing the cups.

FIG. 13 shows, sectionally, the device used in the device FIG. 2 to distribute into each of the cups ofa section of the turntable blood taken from a tube containing a sample.

FIG. 14 is a vertical section along line XIV-XIV of FIG. 13.

FIG. 15 shows, magnified and in cross section, a detail of the device to control the angular movements of a turn-table to feed the cups, sector by sector.

FIG. 16 is a schematic view in perspective showing probes in position to take a sampling.

FIG. 17 shows the same probes ready to feed the above mentioned grooves.

FIG. I8 shows, diagrammatically, a device ensuring the transfer, one after the other, of each of the discs to bring them in turn to the various positions: centrifuge, agitator and photometric reading unit; to make it easier to interpret this figure, the turn-tables holding the discs in each position are not shown.

FIG. 19 is a vertical section of the device shown in FIG. 18 with cross sections.

FIGS. 20 to 23 are horizontal sections ofa cup, showing reactions at various phases of the mechanical treatment of a sample contained in a cup.

FIGS. 24 to 27 are vertical sections corresponding to FIGS. 20 to 23 respectively.

FIG. 28 shows, in perspective, a preferential alternative off the device of FIG. 2.

FIG. 29 is a drawing showing the operation of the device of FIG. 28.

FIG. 30 is a vertical section of an optical element used with one of the cups in a sector of a disc during the reading of the characteristics of the reaction of the sample contained in the said cup, this optical element being for use in nephelometric measurements on the peripheral zone of the reaction.

FIG. 31 is a vertical section of an optical element suitable for use in opacimetric measurements either in the central zone or in the peripheral zone of the reaction.

FIG. 32 is a cross section showing part of a sealing sheet used in the element represented on FIG. 31 (or FIG. 30) making it possible to work in one or other of the reaction zones.

FIG. 33 shows an alternative for the photometric reader.

FIG. 34 is a synoptic diagram of the electronic measuring and interpreting device.

The equipment in general described in these figures is such that it becomes practically impossible to make any error of interpretation of results of analyses. Before printing or punching onto cards or tape the group of results for a given subject, a write-out unit attached to the equipment must compare with the greatest safety possible with automation, all the numbers of the various identification documents (counterfoils and cards) and note that they are identical.

For this reason, full benefits can be derived from this system as a whole only by using sample tubes 6 forming an integral part of a special kit as shown in FIG. 1.

Sampling methods can be varied:

for example: using needles and nozzles, glass bottle,

glass tube or: plastics material bag 1 single or double with nozzle and needle 5.

Such a device has been shown in FIG. 1 to which has been added, to increase the safety factor, an integral system with sample tube 6, cards and counterfoils with identification numbers pre-printed and pre-perforated in the factory.

Tube 6 is connected to vessel 1 by a kind ofmechanographical car strip with removable sections 8, 9 and each having the same identification number (pre-printed and pre-perforated in the factory).

Part 8 adheres to container 1, part 9 adheres to tube 6 and part 10 can be taken off and filed.

It will be seen later that this detachable part 10 can be used in a print-out and electronic unit which can be added advantageously to the equipment to be described in order to carry out various automatic control operations.

After being filled tube 6 is separated from container 1 to which part 8 remains attached. This tube together with part 10 is sent to the laboratory for analysis and this can be some considerable distance away.

On their arrival in the laboratory the various tubes of samples 6 to be analysed are sorted and classified according to certain imperatives. Each tube is sorted and classified manually then placed on a circular stand 11 (FIG. 2) when part 10 is removed. These parts of the labels 10 are classified in consecutive order in the same way as the tubes are placed on stand II.

To facilitate things, stand 11 has around its edge a circular ridge 12 (FIGS. 4 to 6) from which extend at regular intervals lugs or pillars 13 at right angles to said stand and such that they provide two resting surfaces 14 at the top.

Each tube 6 is a plastic injected material and moulded so that it has a vertical extension or tongue (FIGS. 3 and 6) cut out as at 15a and integral with tube 6 at the top, as shown in 15b. This tongue 15 extends parallel to the tube 6 at a distance from it equal to the thickness of pillars 13.

It is on this tongue 15 that card 9 referred to earlier is attached with clips.

To fix on stand 11 each of the tubes 6 made in this way, tube 6 and tongue 15 are clamped astride two adjoining pillars of stand It and pushed down until the lower part 15b comes to rest against the sides 14 of the pillars.

When right down, the lower part of tongue 15 is inserted in a groove 16 moulded in a ridge 12 in front of pillars 13.

By this method of linking tubes 6 and stand 11 when in position, all tubes 6 will necessarily be of the same height.

The same applies to the various information on each of the labels 9 associated with each of the tubes 6, each of which is on the same plane as the corresponding label on the other tubes.

Stand 11 is completed by a means to ensure its rotation step by step, that is to produce successive angular displacements corresponding to the distance between axes of two successive tubes. This can be realized by a ratchet device controlled by a magnet feed intermittently at a regular rate; or it can be realized by a motor 17 (FIG. 2) of the step by step type having a pinion 18 connected with a crown gear 19 integral with plate II.

To determine the blood group, the blood sample contained in each of the tubes 6 each tube corresponding to an individual must be submitted to a series of reactions the number of which can vary according to the number of features required.

For this, from each of the tubes 6 a quantity of blood sufficient to be distributed among a group of cups each containing a special reagent (serum or test cells) must be removed.

In the apparatus according to the invention, the number of cups is twelve for each tube 6, ensuring an hourly output of groupings suitable for a very large specialized laboratory.

These cups are grouped on a stand having the shape of a disc 20 (FIG. 2), this disc being divided into sixteen sectors 21 in each of which is fitted a group of twelve cups 22 corresponding to one tube 6. Thus, these cups are set in various groups on the discs, so that each group contains a number of cups (twelve in the example chosen) equal to the number of reactions to be carried out on a given substance to be analyzed, all

the cups of a group being destined to receive the same substance to be analyzed and each group being replaceable by another group by rotation of a given fraction of a turn of the disc round its centre. This disc can also hold, as indicated below, mixing vessels, grooves and shutters between these vessels and grooves.

Referring to FIG. 7, it can be seen that the twelve cups are distributed along two radial lines 23 and 24 five in one line 23 and seven in the other 24.

In each segment 21, there are two grooves 25 and 26 also radial; groove 25 starts from acylindrical cavity 25a and ends with a wider part 25b placed near the edge of disc 20.

In the same way, groove 26 starts from a cavity 260 and ends at 26b. The cavities 25a and 26a of the grooves form two small cylindrical vessels by which each groove communicates through a vertical slit 0.03 inches (l mm) wide and 0.15 inches (4 mm) long. Referring to FIGS. and 11 showing such a groove said slit can be seen at 25c. At the meeting of groove 25 and vessel 25a there is a housing 250' formed by a simple vertical hold astride the slit, into which a probe 41 can plunge to block, momentarily, slit 250. The liquid is pushed by probe 41 towards the vessel during the blocking phase. The liquids are thus introduced in powerful jets following a descending and tangential direction (as shown by the arrows of FIGS. 10 and 11) in a very compact vessel, mix rapidly and well. When the probe is withdrawn from its housing 25d it unblocks slit 25c and the homogeneous liquid mix contained in vessel 25a passes in a second into the groove.

The inside shape of each cup 22 is generally speaking that of the base ofa retort used in laboratories or more accurately that of a brandy glass."

The cups are, for example, made in two parts, the upper part 27 (FIG. 120) being opaque and black in colour and the lower part 28 being transparent and forming the bottom of the cup.

Sealing off between the two parts 27 and 28 must be assured without sticking (to prevent any risk of leaks and also the risk of asperities forming inside the cups, the inside surface having to be completely smooth) merely by the assembling of the lower part 28 which is of a hard substance such as transparent synthetic resin, for example, known by the name ofPlexiglas (Registered Trade Mark) with the upper part 27 which is of a softer substance, such as polyethylene for example, which material is preferably used to make disc 20 in one piece.

FIG. 12b and 12c show two alternative ways of making the cups where the lower part 28 is placed in a flange 29 with interpenetration of circular ribs from one of the parts in circular notches of the other.

The flanges 29 of each cup are thin and are only made to withstand the forces resulting from the increase of their diameter when the lower hard part 28 is pushed down. if these forces were transmitted to the mass of disc 20, they would bend this upwards by pressing all on the inner face of the disc without any compensating force on the upper face. If this occurred, means would have to be taken to remedy this, which would complicate the moulding of the discs.

Experiments have shown that one way of obtaining very good results is to use cups having the following dimcnsions;

-max. internal diameter of the cup around 0.63 inches 16 mms admissible values between l2 and 20 mms -diameter of upper opening of cup approximately 8 mms -height of cup approximately 20 mms.

The taking of cells and plasma contained in a sample tube 6, introducing them in each of the twelve cups set apart for this tube and the distribution in each of these twelve cups of test reagents (for example test serums and test cells) is done for example by using pumps known as Hook and Tucker Mark I and Mark ll and also as auto-diluter.

Each of these pumps has two automatic syringes, fitted with sluices and flexible tubing.

The first syringe is only used to suck in a small amount of the sample into a fine probe. The second, whose piston is coupled mechanically to that of the first syringe, serves:

1. to take into a small bottle a certain amount of liquid containing reagents, diluent and flush water;

2. to push back this intake of liquid into the probe which was used to take the sample.

The mass of liquid, therefore. coming from this probe, contains: the sample, the reagent and the diluem. The volume of these two last products is sufficient, under certain conditions to rinse the probe internally. These pumps are particularly suitable for use in conjunction with the apparatus being described.

The disc on which the cups are to be loaded is upheld by a drum 30 (FIGS. 2, 13 and 14); it is placed under a platen 31 fixed to the frame of the machine. Two columns 32 integral with platen 31 serve as guides to a sheet 33 which can be moved vertically by means of a cam 34 wedged on an axis 35 driven by a motor 36. On sheet 33 is mounted on a pivot, at 37, an arm 38 having at one end a spindle 39 in contact with a cam 40 also wedged on axis 35 of motor 36. At the other end, arm 38 supports two thin probes 41 and 42 (see also FIGS. 16 and 17). These two probes will henceforth be called primary probes."

Vertically mobile sheet 33 contains twelve thin probes divided into two groups 43 and 44 according to the distribution of the twelve cups 22 in one of the sectors 21 of disc 20 (see FIG. 8). These 12 probes will henceforth be called secondary probes."

At the end opposite to the motor 36, shaft 35 is integral with a pinion 45 engaged with a pinion 46 integral with a cam 47 against which is maintained elastically an arm 48 rotating about 49 on the fixed platen 31 and bearing at its free end a retractable rack 50, the use of which will be indicated later.

Disc 20 during loading is placed in the drum 30 in such a way that one of its sectors 21, for example sector N, is under the mobile sheet 33 in a position suitable for groove 25 of this sector to be beneath probes 43, whereas groove 26 is beneath probes 44.

In FIGS. 13, arm 38 is represented in a position where the two primary probes 41 and 42 are placed over the opening of a sample tube, for example tube 60. The profile of cam 40 (against which rests spindle 39 held by arm 38) is such that, for one turn of the cam, arm 38 moves as shown in 51 of FIG. 13 and carries out a return movement with a stop at each end of the said path.

The first movement of arm 38 brings the primary probes in position above tube 6a in such a way that probe 41 and the entry a of groove 25 of sector N preceding sector N in direction F. are equidistant from pivot 37 whereas probe 42 and entry 26a of groove 26 (FIG. 17) are also equidistant from pivot 37.

The return movement brings the probes back to their original position.

The working of this device is as follows:

Sheet 33 is, at the beginning of the cycle, in a high position as shown in 33a of FIG. 14.

At the beginning of the rotation, cam 34 causes sheet 33 to be lowered and, therefore, primary probes 41 and 42 enter into the sample tube 6.

Probe 42 used for taking a sample of the plasma floating over the residue of cells in tube 6 can slide in a stand 152. Probe 41 is fixed on arm 38.

When sheet 33 is lowered the horizontal part 153 of probe 42 comes against the fixed stop 154. Thus probe 42 is immobilised in a well defined vertical position in relation to tube 6.

Probe 41 continues its movement of descent and at the end of the run of sheet 33 the openings of the probes are at different levels as shown in FIG. 16, these levels being adjustable. Thus, probe 41 plunges into mass M of the settled cells at the bottom of tube 6, whereas probe 42 plunges into the plasma P floating on top of the mass of the said cells.

With the lowering of sheet 33, the secondary probes 43 plunge into groove 25 of the above-mentioned sector N and probes 44 plunge into groove 26 of the said sector.

The pumps are set in motion and produce, on the one hand, the taking up by suction of a given volume of cells into probe 41, of plasma into probe 42 and, on the other hand, the suction of a suspension of cells from groove 25 and of plasma more or less diluted as described above from groove 26, these grooves of sector N having been filled through a previous operation during which time taking of blood by the primary probes 41 and 42 had been made from tube 60 preceding tube 6a (FIG. 14).

After suction of the intakes, sheet 33 begins its rise to return to position 33a. During this rise probe 42 is brought to the same level as probe 41 through the action of spring 155 (FIGS. 16 and 17). At the same time, through action of arm 48 the rack of which 50 rests against a spigot 52 of drum 30, disc 20 is displaced angularly in the direction F (FIG. 13). Turntable 11 carrying the sample tubes 6 is also moved angularly in direction F either by means of its own mechanism (motor 17) or by means of a direct mechanical link with drum 30, for example a crown gear.

During the early part of the rotation of drum and turn-table 11, the edge of the opening of tube 6a and the edges of grooves 25 and 26 rub delicately on the lower ends of probes 41, 42 and 43, 44 respectively before these probes are too high up, in order to remove any droplets which might occur.

Arm 38 is then driven to carry out the movement 51 bringing thus primary probes 41 and 42 above openings 25a and 26a respectively of grooves 25 and 26 of sector N preceding sector N (FIG. 13). Towards the end of run 51 an adjustable screw 156 fixed on probe 42 comes into contact with a fixed stop 157 producing an angular movement of probe 42 in opposition to the effect of relese exercised by spring 155.

The two probes 41 and 42 are separated one from the other and their ends are then placed perpendicularly to openings 25a, 26a of grooves 25 and 26 respectively (FIG. 17), or more exactly over the housings as shown in 25d for groove 25 (FIGS. 10 and 11). The angular movement of drum 30 and therefore of disc 20 is then stopped.

Sheet 33 goes downwards again, so that probes 41 and 42 plunge into the openings 25a, 26a of the grooves 25 and 26 of sector N and probes 43 and 44 plunge into the l2 cups 22 distributed in sector N of the disc.

The pumps then come into action to push out the contents of probes 41, 42 in grooves of Sector N and of probes 43 and 44 into the cups of sector N.

Then sheet 33 comes up and drum 30 resumes its movement which ends when sector N has come into the position previously occupied by sector N. During this rotation, probes 41, 42 are brushed by the edges of the grooves and probes 43, 44 by the edges of the cups.

After drum 30 comes to a standstill, arm 38 is brought back to its original position and probes 41 and 42 are then displayed over a new sample tube, such as tube 6c, which has been brought into the position previously occupied by tube 6a.

After sixteen cycles similar to the one just described, the one disc is completely loaded, drum 30 having made a complete turn.

During loading disc 20 is resting on five similar discs, 20a, 20b, 20c. 20d and 20a (FIG. 14) already loaded and stacked in drum 30.

The stacking of the discs is maintained in the drum by means of sliding thrust blocks 53, diametrically opposed each having a mass of soft iron which, when the drum has made a complete turn (that is when the loading of disc 20 is completed) are set facing magnets 54. When the latter are energised they attract the thrust blocks 53 and these, on sliding, free the lower disc 20a of the stack, a device of the type known as *delivery" holding the disc placed above 20b when this one has fallen by gravity and replaced disc 20a and this continues until thrust blocks 53 freed from the action of the magnets 54 are brought by elasticity back to their place inside drum 30.

A new disc is put manually into the loading position replacing disc 20 which has now taken the place of disc 20c.

The time required for a disc to go from loading position (disc 20 of FIG. 14) to clearance position for re moval from the drum (disc 20a) is determined in such a way that during this time the action of certain rea gents can take place in the cups of the discs.

Disc 20a, freed by thrust blocks 53, falls on to turntable 55 (FIGS. 14, 18 and 19) having a central stud 56 with conical end and fitted with a radial spigot with lean-to ridge 57 which fits into a radial rib 58 of each of the discs 20 (FIGS. 7 and 8), which ensures that disc 20 on the turn-table 55 remains in a well-defined angular position so that each stage follows in the order of loading of each of the sectors, these, as has been said,

corresponding to a sample tube 6 specified and classitied in order on turn-table 11.

Turn-table 55 is connected through its shaft 58 to a motor 59, which is hung vertically at three points to a frame 61, these three connecting points being formed by flexible elements such as rubber so that suspension is not rigid. Because motor 59 is very heavy, the whole assembly of motor car turn table has a low centre of gravity and the system as a whole has a very different period of oscillation than that of the stable regime of the motor revolving at. say, a thousand rpm.

This unit forms a centrifuge. Each of the discs coming in turn on to turn-table S is spun for two minutes of which one minute is at a thousand rpm; a link brake 62 driven by a magnet 63 (FIGS. 18 and 19) stops the centrifuge within five to six seconds and then a vertically movable stop 64 is raised to lie in the path traced out by a spigot 65 integral with turntable 55 (FIGS. 14 and 19). A long impulse is then sent to motor 59 to make turn-table 55 revolve slowly and then stop in the positioned defined by the meeting of spigot 65 and stop 64.

In this specific position, sector N which was loaded first on the disc just spun will be first to pass to a machine for reading reactions as shown later, as the disc cannot turn around its axis before this has been done.

This positioning is accurately adjusted by moving angularly spigot 57 in relation to turn-table 55, that is to say by turning the central stud in relation to the turntable and by then blocking the stud on the turn-table by means of a nut 66 which screws on to shaft 58 of motor 59 (FIG. 19).

As each disc is positioned on turn-table 55 of the centrifugal unit the contents of each cup (0.5 ml. ofliquid max.) present themselves as shown in FIGS. to 24, the cells in suspension in the liquid being regularly dispersed within it During the spinning, the liquid 67 is pressed in the peripheral side swelling of each cup and the particles with sufficient density form a clot as shown at 68 FIGS. 21 and 25.

This spinning is to facilitate as far as possible the possible agglutination of cells by molecular links, reducing, (by compression) the inter-cellular space as much as possible.

During the spinning, the liquid in excess remaining in grooves and 26 is retained in these by a flange 69 set around the disc (FIGS. 7, 8 and 14), unless this excess liquid is sucked up by a special pump.

The centrifugal unit is placed in the middle of a mobile frame having the general shape of the letter H, that is with two parallel frames 70 joined by a cross section 71.

Each of these frames holds an endless chain 72 mounted on wheels 73 placed at the ends of the frame. Each of these chains is connected to a wheel 74. The two wheels 74 are set on a single shaft 75 driven by a motor 76, wheel, shaft and motor being supported by clamps 77 integral with each of the frames 70.

The motor 76 can rotate in both directions and is of the brake-motor type.

Rollers 78 ensure a good contact between chains 72 and driving wheels 74 and rollers 78a can be fitted to support the upper strand of the chain.

Cross section 71 joining the two frames 70 is integral with a threaded vertical column 79 set in a nut 80 maintained vertical between two cross sections 81 integral with the fixed frame of the apparatus, which will be called the transfer gear.

Nut 80 is integral with a wheel 82 connected to an endless screw 83 driven by a motor 84.

Thus when said motor is started screw 79 moves up or down according to the rotation of the motor. Therefore the mobile frame 70-71 is moved vertically in one direction or the other; the guiding columns 85 (not shown in FIG. 19) are placed to counteract the horizontal rotation of the said frame which might result from the screwing movementv The separation of the two chains 72 is determined to that two diametrically opposed segments of the disc resting on turn-table 55 are perpendicular to the chains as shown in FIG. 18.

Therefore by inducing, through the starting up of motor 84, the rise of the mobile frame 70-71, the chains 72 of this frame come up to disc 20a (FIGS. 18 and 19) and drive it by their movement freeing it from the central stud 56 of turntable 55.

When motor 76 is started this drives chains 72 in direction f for the time required for the disc to come over a turn-table 86 placed beyond turn-table 55 in the centre plane of the frame of the transfer gear.

The motor 76 is then stopped while motor 84 starts and turns so as to bring down frames 70 and therefore chains 72. The disc transferred over turn-table 86 comes to rest on it centering on the central stud 87 with radial spigot 88 which, by entering into notch 58 of the disc, ensures that the disc is retained in the same angular position as that which it occupied on turn-table 55.

Shaft 89 integral with turn-table 86 is fixed to a sheet 90 (FIGS. 18 and 19) connected by four spindles 91 to four small crank-discs 92 with vertical shafts set on the fixed frame of the machine.

Shaft 93 of one of these crank-discs is integral with a pulley 94 and shaft 95 of another crank-disc is integral with another pulley 96. Pulleys 94 and 96 are facing each other, pulley 94 has a diameter approximately three times that of pulley 96.

Between the two pulleys is placed the end of shaft 97 of a motor 98 supported on a cradle 99 pivoting in 99a on the frame of the machine, this cradle being extended beyond its pivot 99a and having at one end a screw 100 in contact with a cam I01. Being mounted with a pivot on the prongs of cradle 99, motor 98 is maintained by its own weight in position as shown FIG. 19, the end of the shaft resting against the edge of pulley 94. In this position motor 98 rests on one end of a lever 102 pivoting at 103 on the fixed frame of the machine. The other end of lever 102 rests on the core of a solenoid I04 fixed to the frame.

When the solenoid 104 is energised, its core moves lever 102 to bring motor 98 into a position where the end of shaft 97, now in position 970, is in contact with the small pulley 96 (FIG. 19).

Shaft 97 resting one end against one or other of pulleys 94 or 96, motor 98, when started up, drives by rotation the crank-disc 92 integral with the said pulley.

Sheet 90 transmits this rotating movement to the three other crank-discs and makes circular movements of a radius equal to the distance between each spindle 91 and the rotation-axis of the corresponding crankdisc and this without causing the sheet to turn on itself. Tum-table 96 connected to this sheet naturally has the same circular movement at a slow speed (about 40 to 80 rpm according to the speed of the engine) when shaft 97 is in contact with pulley 94 and at a high speed (about to 200 rpm) when shaft 97 is in contact with pulley 96.

For a given speed of motor 98 it is possible to vary slightly, by increasing, the speed of pulley 94 that is the slow speed of turn-table 86.

Cam 101 is made to turn so that cradle 99 produces a slight rise of motor 98 so that contact between shaft 97 and pulley 94 does not occur at the end 105 with the small diameter of the said shaft but on the conical part 106 (FIG. 19). By regulating screw 100 the point of contact along the generatrix of cone 106 can be adjusted very exactly and the speed required obtained with maximum precision, which is very important for the quality of the further examinations of the reactions.

The rapid movement (pulley 96 driving) stirs up the liquid mass, contained in each of the cups 22, imparting a circular movement in the same direction as that of the rotation of turn-table 86 of the agitator device. This liquid covers the deposit of cells settled on theh side of each cup (as shown in 68 on FIGS. 2I and and brings back into suspension both the cells still free (not agglutinated) and the cells agglutinated in particles of various sizes as shown in 107 FIGS. 22 and 26.

The slow movement (pulley 94 driven by end 105) induces by a complex mechanism the gathering in the central zone of each cup of all agglutinated particles, that is having a greater mass than that of a free cell. Thus at the end of the slow movement, the agglutinated material is placed in the central zone of each cup as shown in 108 FIGS. 23 and 27 and there only re mains in the peripheral annular zone 109 free, non agglutinated cells.

Agitating at a given speed obtained by adjusting screw 100 (pulley 94 driven by the conical part 106) enables a true collection of micro-agglutinates to be made which is very important as specified above.

When the stirring-up stage is ended motor 84 is started so that the mobile frame 70-71 rises as well as the disc by means of chains 72 as said earlier.

With the start of this upward movement the armature of a micro-switch 110 (FIG. 19), placed on the mobile frame, comes against sheet 90 of the agitation device and cuts the feed of the motor 98 at the precise moment when the central stud 87 of turn-table 86 is passing through the point of its trajectory furthest from the central stud 56 of turn-table 55 of the centrifuge.

Turn-table 86 being thus immobilised, chain 72 raise the disc set on the said turn-table and then bring this disc over the third turn-table 11 which follows turntable 86 (FIGS. 18 and 19).

Turn-table 111 is set on a pivot 112 integral with the fixed frame of the machine; this table also has a central stud 113 with radial rib 114. This radial rib 114 is mobile in the vertical plane so that it can close an electric circuit when nothing rests on it, which occurs when the disc is correctly positioned. The apparatus cannot begin reading a disc unless the said electric circuit is complete.

The disc deposited on the turn-table by the lowering of the mobile frame 70-71 interocks with this stud and is then immobilised on the table in the same angular position as it occupied on the previous turn-tables 55 and 86, that is to say that the sector loaded first by the contents of an identitied sample tube will be the first to be subjected to examination of the reactions.

FIG. 28 shows an alternative loading device which has the following advantages over the former described one:

simplification of the construction of discs carrying the cups, since the mixing reservoirs. grooves and sluices connecting these vessels and grooves can be dispensed with;

rinsing of the ducts can be carried out very efficiently and at length if desired;

completely doing away with the need to dismantle the pumps to clean them if they had to dispense products subject to degradation;

greater economy of reagents.

In the layout shown in FIG. 28, one can see, as in the device shown in FIG. 2, the centrifuge 55, the stirrer 86, the reading table III, the transfer device with chains 72 and drum 30 on which turn-table 20 is placed. Turn-table ll on which tubes 6 were placed is done away with. As mentioned above, one of the safety principles of the device according to the invention is to read (by means of reader 148 as described below) and to set down the identification number of each sample tube only when the cups corresponding to this tube are about to pass under the photometer 115 for measuring reactions. It can, however, take up to twenty minutes between the time when a sample is taken from a tube to be poured into a cup on the turn-table to the moment of reading this number. This therefore requires the presence of a large number of samples between the position for taking the sample and the position to read the cards. Turn-table 11 must thus be very large to accommodate a great many samples.

The set-up shown in FIG. 28 obviates this difficulty. To this end, the sample tubes in which the blood to be analysed has been placed are introduced into parallelipipedic loaders 200 which can move, by propulsion means not visible on the figure, in two orthogonal directions on a sorting-table 201 of the apparatus. These movements make it possible to bring the loaders and tubes they contain to various positions where various operations are carried out, as described further on.

As has already been said, reactions cover both erythrocyt and plasma or the serum of the blood to be analysed. However, as it would be difficult to distribute directly and accurately the globular deposit (highly concentrated) in the vessels or cups, it is necessary to prepare a diluted suspension. For this, each sample tube 6 is integral with another tube 6a called auxiliary tube which will be explained later on.

As soon as the blood has been taken from a patient, the sample tube is filled, the auxiliary tube remaining empty. Then the unit formed by these two tubes and their identification tag is placed on one of the loaders 200 which can, for example, hold 16 of these units placed side by side.

When a loader 200 is full, it is placed on the table 201, through a passage or chute 202, where it is made to advance step by step by means not shown to bring the first sample tube of the said loader under probe 203 of another pump 204. Probe 203 is flexible and goes through a mobile sheet 205 (for example by means of cams not represented) able to move it. When the first sample tube 6 is in position probe 203 plunges into the deposit of erythrocytes formed by sedimentation or centrifugation, sucks up a given and adjustable volume of this deposit and rises, rubbing against the inner edge of tube 6. Then probe 203 moves sideways until it is over the associated auxiliary tube 60, into which it descends and ejects completely the sample of erythrocytes taken together with a few millilitres of physiological saline solution which rinses out efficiently the inside of probe 203 as well as the outside, the probe then plunging into the liquid it has just ejected. To this physiologic solution can then be incorporated sensitizing ingredients, such as dextran, bromelin. etc. Probe 203 then rises rubbing against the inner edge of the auxili ary tube 60 and returns to its original position. In this way there is prepared in the auxiliary tube 6:: a globular suspension suitable to obtain later a good photometric precision and a good sensitivity.

Loader 200 then comes forward one step to bring the next tube 6 under probe 203 and the same process repeats.

When the l6 auxiliary tubes of the loader have been filled as said, the loader is moved so as to bring each tube 6 and tube 6a associated under probes 206 and 207 respectively of a peristaltic multiple pump 208 after a sufficient time lag (say 8 minutes) for the ingredients to have acted on the erythrocytes contained in the auxiliary tube 6a.

The peristaltic pump 208 can be of any known make and its outputs are connected to those of another peristaltic pump 209 to form mobile probes with outlets 210 (see FIG. 29) the suction probes 211 of this pump plunging into containers holding reagents 212 set in casing 212a (see FIG. 28).

Of course the number of outlets of pump 209 is equal to the number of reagents used and linkage between outlets of pumps 208 and 209 is obtained to be able to add the appropriate reagents to the sample in tube 6 or to the cell suspension in tube 6a.

Thus on FIG. 29 (where only four outlets to pump 209 instead of the twelve on FIG. 28 have been shown to make the representation clearer] probes 206 and 207 are respectively connected each to two reagent vessels through pumps 208 and 209.

Probes 210 are formed by flexible ducts going through a mobile sheet 213 (for example using cams not represented here) adapted to move them and bring them either into a fixed trough 214 or into cups 22 of a disc 20.

Probes 206 and 207 being respectively plunged into the sample contained in tube 6 and into the cell suspension contained in auxiliary tube 6a, pump 208 starts moving (in the direction of arrow F208) then stops when the taken samples begin to run into the evacuation trough 214, probes 210 being then in it. These probes 210 rise rubbing aginst the edge of the trough 214 and move along to plunge into a group of cups 22 on turn-table while probes 206 and 207 come out of tubes 6 and 6a to plunge and remain in a tank 215 containing renewed physiological saline solution. Pump 208 continues again and lets out into cups 22 either blood sample from tube 6 or the cell suspension from tube 6a. At the same time, pump 209 starts (in the direction of arrow F) and distributes the reagents into cups 22. Then pumps 208 and 209 stop, probes 210 rise rubbing against the edge of the cups into which they were plunged and return to their original position in trough 214. Pump 208 starts up again, rinsing the pipes associated to it with physiologial saline solution from probes 206, 207 to probes 210. The flush water is evacuated into trough 214. After rinsing, pump 208 stops, then probes 206 and 207 come out of tank 215 rubbing against the edges of it and are placed over the tubes 6 and 6a which follow. A new cycle is about to begin.

While probes 210 go from one group of cups just loaded to trough 214, disc 20 turns to replace that group with a new group of empty cups just loaded.

The various movements just described are carried out automatically by means of mechanisms not shown as they are self-evident to the specialist. The cycle of movements of probe 203 and that of the working of pump 204 are synchronized with the cycles of probes 206 and 207, and 210 and pumps 208 and 209, to take the same time as the displacement of loaders 200. After these operations, the loaders advance step by step in two orthogonal directions towards an evacuation chute 216 of table 201.

The identification reader 148 referred to later is situated here. Preferably systems of cams controlling the advance of loaders and discs 20 (following a path similar to that described earlier in respect of the first embodiment are coupled so that the identification number of a pair of tubes 6-62: is read (by 148) and transcribed when disc 20 containing the corresponding reactions reached the reaction reader 115.

Whether the loading device of the cups is that shown FIG. 2 or that shown in FIG. 28, the first sector of the disc resting on turn-table 111 is situated at a reading area" where it is immobilised.

The reading area is situated between two casings, the upper one shown diagrammatically at 115 on FIGS. 2 and 28, the lower one, also shown diagrammatically, 116 on FIGS. 2 and 19.

A claw mechanism, similar to that of some cinematographic projectors and not represented in the drawings, allows the disc to advance directly step by step and to remain for the time needed to carry out a reading. To bring in turn each of the sectors of the disc into position on the reading area, the disc has notches set up in the mould and corresponding exactly to the position of the cups.

This step by step advancing movement of the disc is determined with an exactitude of $0.02 inches (0.5mm) so that each cup is brought into a coaxial position with the corresponding optical device.

When nephelometric means are used to analyse the contents of the cups, the upper casing 115 contains a projector with an iodine bulb (of 600 W) shown diagrammatically at 117 FIG. 30, a condenser, and twelve lenses 118 distributed according to the lay-out of the cups 22 in a sector of disc 20, each lens corresponding to a cup.

Each of these lenses receives light from the bulb 117 through ground glass 119 and each lens forms the image of aperture 120 formed in a stop 121 over the whole surface 122 of each of the reaction mixtures, without lighting directly the inner surface of the upper part 27 of each cup and, moreover, without the beam being intercepted by the upper edge of the cup.

As already said the upper part 27 of the cups can be polyethylene or black polystyrene to form a black background."

Below turn-table 111 which has apertures corresponding to each of the cups in each of the sixteen sectors there is located, inside casing 116, a movable sheet 123 having twelve annular openings 124 (one per cup).

Under each of thes annular openings 124 is placed a tube 125 containing two lenses 126 giving an image of opening 124 on a photoresistive cell 127.

Screens 128 placed to eliminate the parasitic light sent back by the inner wall of the tube are situated along tube 125.

The top of tubes 125 have an annular opening 129 corresponding to opening 124 of sheet 123 and also a central opening 130, the use of which will be shown later.

If opacimetric measurements are used to analyse the contents of the cups the tubes in the lower casing 116 is different to that shown FIG. 30. In such a case (FlG. 3]) tubes 131 containing the photoresistive cell 127 are fitted with two lenses 132, 133. as shown.

A mask 135 (replacing sheet 123 above mentioned) also has annular openings 136 (placed to correspond each to a cup) and also twelve holes 137 also set out in each sector (see FIG. 32).

Plate 135 can be moved at an angle in the horizontal plane under the action of a magnet not shown here. In one position the annular openings 136 cover annular openings 138 in the top of each tube 131 and in another position they close these openings 138 but, then, expose the holes 137 opposite the central openings 139 of the base 134.

In these conditions the machine makes readings which refer only to a small central zone of each reaction.

The size of the annular openings 136 and 138 are greater than those of the openings 124 and 129 respectively (FIG. 30) which is an advantage.

After the period of agitation, carried out on turntable 86 there only remains in a peripheral annular zone, shown as 109 in FIGS. 23 and 27 free non agglutinated cells which give to this peripheral liquid zone of the reaction a cloudiness which can be measured photometrically:

either by nephelometric means if a very small amount of reagent cells have been used or by opacimetric measurements if a fairly strong dose of cells has been used.

Nephelometry with peripheral reading can be carried out if the disc is of a black, opaque substance and if a sheet 123 (FIG. 30) with annular openings 124 is used.

Opacimetry (or if desired, a measure of peripheral transmission) can be carried out if the disc is either of a black substance, or transparent or translucent or opaline and a sheet 123 is used (FIG. 30).

Opacimetry with central reading can be carried out whatever the disc but with a sheet 135 using holes 137.

Opacimetry of the central zone of a reaction can be carried out with a device as shown FIG. 30. in such a case the central opening 130 is used.

The 12 cells 127 corresponding to the 12 cups of a sector of the disc are connected by a cable 140 to 24 conductors, to an electronic set-up represented diagrammatically in FIG. 2 and including elements already known as of right and therefore not described in any detail. These elements are:

12 bridges used to equalize the characteristics of cells a programmer-interrogator 141 a digital voltmeter 142 a system of threshold gates 143 a memory block 144 a cornparer of coded signals (alpha-digital) a printer control unit Each of the l2 cells is mounted in a bridge so that a zero adjustment and a sensitivity adjustment are possible. The cells are fed by a continuous regulated voltage applied permanently.

The programmer-interrogator 141 connects in turn (possible) out of phase balance voltage of the bridges to a voltmeter 142 having three decades. If desired, the numbers all three decades may be taken into account; or from two decades only, or from one, and these values will then be compared to standard values to determine the characteristics of the reaction being examined.

The electronic device has the advantage of giving a means of using the printer units.

In such a case the information derived from the digital voltmeter 142 will be transmitted to the system of threshold gates 143.

As seen below, each measurement of the digital voltmeter 142 can be compared (for example with prese lection counters) to the threshold levels, each adjusted by a ten level numerical decade.

If the measurements by the voltmeter 142 is within the two threshold levels, the printing on the printer 143 comes out in red. In all other causes it will be black.

Also a memory 144 with three positions is engaged according to the position of the measurement result compared with two threshold levels, namely:

measurement equal or greater than the lower level measurement equal or greater than the upper level measurement between these two levels.

Switching is done by the programmer-interrogator 141 through relays.

The apparatus has several programmes, plug-in or interchangeable, which can be started by means of a manual selector button or by an automatic selector controlled by a coloured filter placed on a window set there for this purpose on the discs.

This filter with narrow transmission band passes over a group of cells each fitted with a narrow transmission band filter which is different for each cell; only the carrier cell of the filter of the same colour as that of the filter situated on the disc will be energized and will start up the special corresponding programme.

The results calculated from the measurements can evaluated in three different ways:

absolute measurement of a cell relative measurement of one cell compared with another cell taken as reference 0 average between absolute measurements of several cells (generally six).

Each measurement will give rise to the printing of a quantitative result (by printer and possibly by a card punch 146 (FIG. 34).

After a cycle of examination of twelve cells the memories corresponding to each of these twelve cells are in various positions." To some of the possible combinations of these positions is made to correspond, on the printer, certain characters or sequence of characters.

Thus an automatic interpretation of the results is obtained. 

1. AS A MECHANICAL SUBASSEMBLY OF A LIQUID CHEMICAL OR BIOCHEMICAL ANALYZING MACHINE, A SUPPORT FOR A MULTIPLICITY OF VESSELS ADAPTED TO CONTAIN LIQUID SAMPLES COMPRISING: AN ANNULAR SUBSTANTIALLY PLANAR SHAPE MEMBER HAVING A CENTRAL OPENING THEREIN, SAID MEMBER DEFINING A MULTIPLICITY OF APERTURES EACH ADAPTED TO RECEIVE AND POSITIVELY TO MAINTAIN A VESSEL, SAID APERTURES BEING DISPOSED ANGULARLY AND RADIALLY ON SAID MEMBER THROUGHOUT SUBSTANTIALLY THE ENTIRE AREA THEREOF, SAID MULTIPLICITY OF APERTURES BEING FORMED IN GROUPS OF APERTURES, THE APERATURES OF EACH GROUP BEING SPACED ALONG A RESPECTIVE LINE OF A PLURLITY OF LINES EXTENDING RADIALLY FROM THE CENTER OF SAID MEMBER TO THE PERIPHERY THEREOF. VESSELS IN SAID APERTURES, EACH VESSEL HAVING AN AXIS OF SYMMETRY OF REVOLUTION AND A TRANSPARENT CONCAVE BOTTOM, EACH VESSELS'' SHAPE BEING SUBSTANTIALLY THAT OF A CUPOLA CONNECTED TO OPAQUE SIDE WALLS INCLINED RELATIVE TO THE AXIS OF SYMMETRY OF SAID VESSEL WITH EACH VESSEL HAVING A BULBOUS PORTION ADJACENT THE BOTTOM THEREOF, AND MEANS ON SAID MEMBER FOR ANGULARLY POSITIONING SAID MEMBER WITH RESPECT TO A SHAFT OF SAID MACHINE ADAPTED TO PASS THROUGH SAID CENTRAL OPENING.
 2. As a mechanical subassembly of a liquid chemical or biochemical analyzing machine, a support for a multiplicity of vessels adapted to contain liquid samples comprising: an annular substantially planar shaped member having a central opening therein, such member defining a multiplicity of apertures each adapted to receive and positively to maintain a vessel, said spertures being disposed angularly and radially on said member throughout substantially the entire area thereof, said multiplicity of apertures being formed in groups of apertures, the apertures of each group being spaced along a pair of next adjacent lines of a plurality of lines extending radially from the center of said member to the periphery thereof, vessels in said apertures, each vessel having an axis of symmetry of revolution and a transparent concave bottom, each vessels'' shape being substantially that of a cupola connected to opaque side walls inclined relative of the axis of symmetry of said vessel with each vessel having a bulbous portion adjacent the bottom thereof, and means on said member for angularly positioning said member with respect to a shaft of said machine adapted to pass through said central opening. 